| 第 48 卷第 2 期 |  | Vol. 48 No. 2 | | 2018 年 4 月 | Apr 2018 |
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所屬欄目：醫藥及中間體
達格列凈的合成研究 |
| 呂久安1，范龍濤2，張克軍1，徐少婕2，彭效明2，居瑞軍2，晁建平2*
（1. 北京紅惠新醫藥科技有限公司 北京 102600；2. 北京石油化工學(xué)院 北京 102600） |
| 摘 要：以5-溴-2-氯-4'-乙氧基二苯甲烷為原料，經(jīng)過(guò)縮合反應得到2-氯-5-（1-甲氧基-D-吡喃葡萄糖-1-基）-4'-乙氧基二苯甲烷，除去甲氧基得達格列凈粗品，然后通過(guò)上乙�；�、重結晶除去異構體，后再脫乙�；眉兌容^高的達格列凈，最后再與S-丙二醇成溶劑化合物，得到目標晶型產(chǎn)物。達格列凈產(chǎn)品單雜小于0.1%，純度大于99.5%。產(chǎn)物經(jīng)過(guò)ESI-MS、1H NMR、熱分析、X-粉末衍射確證。 |
| 關(guān)鍵詞：達格列凈；5-溴-2-氯苯甲酸；D-葡萄糖酸內酯 |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：1009-9212（2018）02-0033-03 |
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| Synthetic of Dapagliflozin |
| L?譈 Jiu-an1, FAN Long-tao2, ZHANG Ke-jun1, XU Shao-jie2, PENG Xiao-ming2, JU Rui-jun2, CHAO Jian-ping2*
(1. Beijing Honghui Meditech Co., Ltd., Beijing 102600, China; 2. Beijing Institute of Petrochemical Technology, Beijing 102600, China) |
| Abstract：2-Chloro-5-(1-methoxy-D-glucopyranosyl-1)-4'-ethoxydiphenylmethane was obtained from a condensation reaction using 5-bromo-2-chloro-4'-ethoxy diphenyl methane as the starting material. The crude Dagliflozin was obtained by removing methoxyl group. Acetyl groups were introduced to the Dagliflozin and isomers were separated by recrystallization. Higher purity dapagliflozin was achieved by removing acetyl groups, followed by mixing with S-propanediol as a solvent compound to obtain the desired crystalline product. The target product was confirmed by ESI-MS, 1H NMR, thermal analysis and X-ray powder diffraction. Dapaglifloxzin was obtained with a single impurity of less than 0.1% and a purity of greater than 99.5%. |
| Key words：dapagliflozin; 5-bromo-2-chlorobenzoic acid; D-gluconolactone |
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基金項目：國家自然科學(xué)基金項目（21406015）。
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作者簡(jiǎn)介：呂久安（1983-），男，遼寧海城人，工程師，研究方向：藥物合成與質(zhì)量控制（E-mail：jiuan.lv@mail.honghui-meditech.com）。
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聯(lián) 系 人：晁建平，副教授，研究方向：藥物合成工藝研究（E-mail：chaojp@bipt.edu.cn）。
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收稿日期：2018-04-20
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